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Bone modifying agents and multikinase inhibitors as treatments for chordoma: A TriNetX-based retrospective cohort
Kamal Shaik1, Spencer Rasmussen1, Rudy Rahme2
1Department of Neurosurgery, Drexel University College of Medicine, Philadelphia, PA 19104, USA.
Introduction:
Chordomas are rare malignant tumors arising from embryonic remnants of the notochord, most commonly affecting the axial skeleton. Although advances have been made in surgical resection and radiation therapy, systemic treatment options remain limited. Bone-modifying agents (BMAs), including zoledronic acid and denosumab, as well as multikinase inhibitors (MKIs) like lenvatinib and cabozantinib, have emerged as potential targeted therapies based on preclinical models. However, comparative real-world data evaluating their outcomes in chordoma patients is lacking.
Methods:
A retrospective cohort study was conducted using the TriNetX Research Network. Patients with chordoma (ICD-10-CM C41.0, C41.2, C41.4) were stratified into treatment groups based on receipt of zoledronic acid, denosumab, or multikinase inhibitors (MKIs). Propensity score matching was used to adjust for baseline confounders. Outcomes evaluated at 5 years post-diagnosis included all-cause mortality, pathologic fracture, spinal cord compression, and osteonecrosis. Risk ratios with 95 % confidence intervals were calculated.
Results:
Compared to denosumab, zoledronic acid was associated with a higher 5-year mortality risk, but a lower osteonecrosis risk. Comparisons involving MKIs showed no difference in mortality. No pathologic fractures were reported across cohorts. Spinal cord compression was not different among treatments.
Conclusion:
This study highlights potential differences in survival and skeletal-related outcomes among chordoma patients treated with BMAs, specifically denosumab and MKIs. These preliminary findings underscore the need for prospective studies to better define optimal systemic therapies for this rare malignancy.
Insights
Zoledronic acid showed higher mortality but lower osteonecrosis risk compared to denosumab in chordoma patients. Multikinase inhibitors had no impact on mortality, highlighting varied outcomes for systemic therapies in rare bone cancers.
Area of Science:
- Oncology
- Orthopedic Oncology
- Pharmacology
Background:
- Chordomas are rare axial skeleton malignancies with limited systemic treatment options.
- Bone-modifying agents (BMAs) and multikinase inhibitors (MKIs) show preclinical promise.
- Real-world comparative data on these targeted therapies for chordoma is scarce.
Purpose of the Study:
- To compare the real-world effectiveness of zoledronic acid, denosumab, and MKIs in chordoma patients.
- To evaluate survival and skeletal-related outcomes at 5 years post-diagnosis.
- To inform future systemic therapy strategies for chordoma.
Main Methods:
- Retrospective cohort study using the TriNetX Research Network.
- Chordoma patients stratified by zoledronic acid, denosumab, or MKI treatment.
- Propensity score matching used to control for confounders; outcomes analyzed at 5 years.
Main Results:
- Zoledronic acid linked to higher 5-year mortality and lower osteonecrosis risk versus denosumab.
- MKIs demonstrated no significant difference in mortality compared to BMAs.
- No significant differences observed in pathologic fracture or spinal cord compression rates across treatment groups.
Conclusions:
- Significant differences exist in survival and skeletal outcomes between BMAs (zoledronic acid vs. denosumab) in chordoma.
- Current data suggests MKIs may not offer survival benefits over BMAs.
- Prospective studies are crucial to establish optimal systemic treatment protocols for chordoma.
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